title: Temporal reduction of LATS kinases in the early preimplantation embryo prevents ICM lineage differentiation.
abstract: Cellular localization of the Yes-associated protein (YAP) is dependent on large tumor suppressor (LATS) kinase activity and initiates lineage specification in the preimplantation embryo. We temporally reduced LATS activity to disrupt this early event, allowing its reactivation at later stages. This interference resulted in an irreversible lineage misspecification and aberrant polarization of the inner cell mass (ICM). Complementation experiments revealed that neither epiblast nor primitive endoderm can be established from these ICMs. We therefore conclude that precisely timed YAP localization in early morulae is essential to prevent trophectoderm marker expression in, and lineage specification of, the ICM.
authors.affiliation: Mammalian Development Laboratory, Institute of Medical Biology, Singapore. chanchao.cl@gmail.com
authors.forename: Chanchao
authors.initials: C
authors.lastname: Lorthongpanich
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Messerschmidt
authors.forename: Siew Wee
authors.initials: SW
authors.lastname: Chan
authors.forename: Wanjin
authors.initials: W
authors.lastname: Hong
authors.forename: Barbara B
authors.initials: BB
authors.lastname: Knowles
authors.forename: Davor
authors.initials: D
authors.lastname: Solter
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D001755:Blastocyst / Q000166:cytology*; D053624:Blastocyst Inner Cell Mass / Q000166:cytology*; D018797:Cell Cycle Proteins; D002454:Cell Differentiation; D019070:Cell Lineage; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D005816:Genetic Complementation Test; D000090683:Hippo Signaling Pathway; D051379:Mice; D010750:Phosphoproteins / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D010750:Phosphoproteins; D000091102:YAP-Signaling Proteins; C486223:Yap1 protein, mouse; C490501:Lats1 protein, mouse; D017346:Protein Serine-Threonine Kinases
keywords: Hippo pathway; LATS; inner cell mass; lineage specification; trophectoderm